The long-term goal of this application is to develop mannan derived from Baker's yeast as asthma therapy. The limitations of currently available immunomodulators are their toxicity at higher doses and the lack of beneficial effect on airway smooth muscle (ASM) remodeling and therefore, new adjunctive therapeutics are needed. Initial findings in the P.I.'s laboratory have shown that mannan from S. cerevisiae, a carbohydrate-based prebiotic polymannose agent, inhibits airway inflammation, hyperreactivity (AHR) and ASM remodeling. Our central hypothesis is that mannan from S. cerevisiae is a novel class of immunomodulator that suppresses ASM remodeling. Studies are proposed 1) to determine the optimum dose and dose timing of mannan administered intranasally. 2) to determine the optimum dose and dose timining of mannan administered orally. The University of Tennessee College of Medicine Department of Pediatric Allergy/Immunology and Cumberland Emerging Technologies Inc (CET), an affiliate of Cumberland Pharmaceuticals Inc (CPI), are collaborating to identify and develop promising pharmaceutical therapies for treating and preventing asthma. The P.I. will conduct preclinical studies outlined in the proposal and CET will develop the product for the preclinical and clinical trials. The knowledge gained from these studies will provide a novel class of adjuctive asthma therapy that will modulate ASM remodeling and will lead to a unique intranasal and oral products that will benefit asthmatics and patients with other related diseases. PUBLIC HEALTH RELEVANCE: Our central hypothesis is that mannan from S. cerevisiae is a novel class of immunomodulator that suppresses ASM remodeling. The long-term goal of this application is to develop mannan derived from Baker's yeast as asthma therapy.